Hypocalcemia in traumatic brain injury: Pooled prevalence and narrative synthesis of associations with injury severity and early clinical outcomes - a systematic review and Meta-analysis

Abstract

Objective: To determine the prevalence of hypocalcemia and synthesize its reported associations with injury severity and early clinical outcomes in patients with traumatic brain injury (TBI). Methods: A systematic review and exploratory meta-analysis of observational studies reporting hypocalcemia in TBI was performed. A random-effects meta-analysis using restricted maximum-likelihood estimation was per formed on logit-transformed proportions. Because substantial clinical and methodological heterogeneity was anticipated, the pooled estimate was interpreted as exploratory. Publication bias and small-study effects were assessed using Egger's regression, Kendall's Tau, and funnel-plot inspection. Prespecified subgroup analysis by geographic region and leave-one-out sensitivity analysis were conducted. Associations between hypocalcemia, injury severity, and early clinical outcomes were synthesized narratively. Results: Twelve studies comprising 3485 TBI patients met the inclusion criteria. The exploratory pooled prevalence of hypocalcemia was 39.80% (95% CI: 23.78%–58.35%). Between-study heterogeneity was substantial (I2 =89.86% Q[11] =110.625, Pooled prevalence varied across geographic subgroups, from 29.34% in South Asia to 74.29% in the Qatar/ Romania subgroup. Leave-one-out estimates ranged from 35.40% to 44.96%. Narrative synthesis indicated that hypocalcemia was frequently associated with greater injury severity and adverse early clinical outcomes, although independent prognostic evidence was limited. Conclusions: Hypocalcemia is frequently reported in patients with TBI, but the available evidence is heterogeneous and geographically uneven. The pooled estimate should therefore be considered exploratory rather than a precise global prevalence. Associations with greater injury severity and adverse outcomes were reported in several studies, but causal or independent prognostic conclusions remain uncertain. Future prospective studies should use standardized calcium definitions, report total and ionized calcium separately, obtain serial measurements, and apply multivariable outcome models.